The potential of efferocytosis for the treatment of bronchial asthma: A review of current trends, mechanisms and prospects

Abstract

As a chronic inflammatory disease of the lungs, bronchial asthma is closely associated with three key characteristics: airway inflammation, airway hyperresponsiveness, and airway remodeling. The long-term infiltration of multiple inflammatory cells into the airway interstitium results in damage to the airway epithelial barrier. Macrophages, as the primary immune cells responsible for the clearance of damaged and apoptotic cells from the asthmatic airways, phagocytose asthmatic cells through a series of efferocytosis phases, including the “find me,” “eat me,” and “digest” phases. This process, which involves the phagocytosis of apoptotic inflammatory and epithelial cells, serves to reduce airway epithelial damage and protect immune homeostasis. However, the cytosolic burial process of macrophages in asthma patients often exhibits dysfunctions, including reduced phagocytic efficiency, disorders of cytosolic burial signaling molecules, and the activation of airway inflammation. These impede the clearance process of inflammatory cells from the airway epithelium and necessitate the formation of temporary protective barriers. Barriers are formed through epithelial-mesenchymal transition, which impairs the regenerative capacity of the damaged epithelium and its barrier function, leading to an imbalance in epithelial-mesenchymal homeostasis. This, in turn, results in the occurrence of airway remodeling, which further exacerbates the process of asthma development. Intact and efficient efferocytosis serves as a critical regulatory mechanism in maintaining inflammatory homeostasis and suppressing epithelial-mesenchymal transition. Therapeutic modulation of macrophage-mediated efferocytosis represents a promising strategy for bronchial asthma intervention. In this paper, we present an overview of the specific stages of efferocytosis and the molecular mechanisms underlying the defects in efferocytosis.